The original rabies vaccine of Pasteur, announced in 1885, introduced a new era in medicine. For the first time, it was possible to protect victims of rabid animals from rabies. It was soon realized that the original vaccine, produced in brain tissue, had major disadvantages. The vaccine was very crude, containing high concentrations of neural tissue, lipids, and proteins. Therefore, local and systemic reactions and neuroparalytic accidents were common.
Improved rabies vaccines followed, such as the partially inactivated sheep brain vaccine (1908) and the phenol-inactivated rabbit brain vaccine (1911). Both of these vaccines still caused a significant number of neuroparalytic involvements.
In about 1955, the duck embryo vaccine largely replaced the neural tissue vaccines for human vaccination against rabies in the United States. Neuroparalytic involvements have been virtually eliminated by the embryo vaccine, but local and systemic reactions still occur because of the proteins and lipids in the vaccine.
Rabies vaccine is now ordinarily produced in duck embryos by the elementary process of growing the vaccine in the embryo, harvesting the embryos when optimum virus titer has been achieved, homogenizing the embryos, passing the homogenate through a fine strainer, adjusting the volume to 1 ml. per 200 mg. of embryo tissue and inactivating the virus. The vaccine contains about 10 percent of solids, practically all of it duck tissue, not virus. Therefore, massive amounts of avian proteins and lipids are in the vaccine as it is administered to the patient.
Anaphylactic shock reactions may occur in the patient in at least two ways. At times the vaccine will cause reactions to occur at the first injection. The reactions will be particularly severe in individuals who are for some reason sensitized to avian tissue. Unfortunately, it is necessary to administer repeated doses of the vaccine for protection. Subjects who are to be immunized before exposure must be initially vaccinated with a number of injections of vaccine, and with regular booster doses. Unvaccinated patients who have been bitten by a possibly rabid animal must be vaccinated many times within a short period of time, frequently 14-21 daily doses.
Thus, the duck embryo vaccine, which contains much avian tissue, sensitizes the individual. With each successive dose of the vaccine, or other vaccines of avian origin, it is to be expected that the local or systemic reactions could be more severe and more painful.
The common local reaction occurs as a painful inflammation at the site of injection. More serious reactions involve the organ where the antigen and antibody involved accumulate and react. In the human being, the typical severe reaction is failure of the respiratory function and asphyxiation.
Attempts have been made to produce a rabies vaccine by tissue culture methods, which would provide a vaccine almost free of objectionable host tissues. Such methods so far have usually produced only marginally adequate virus titers.
Another approach to a tissue-free vaccine is to purify the vaccine after it is produced in the normal manner. For example, tissue culture vaccines have been purified by means of centrifugation in a gradient-density medium. Anderson, Anal. Biochem. 32, 460 (1968); Lavender et al., Applied Microbiol. 22, 358-65 (1971). The gradient-density process effectively removes the antigenic portion of the vaccine from the lighter and heavier portions. However, it requires very precise operation and highly sophisticated controls on the centrifuge and accessories.